Chronic obstructive pulmonary disease (COPD) is a disease with high morbidity and mortality worldwide, which can cause serious social and economic burdens. Allyl isothiocyanate (AITC) is one of the most common natural isothiocyanates and has been shown to have anti-inflammatory and antioxidant biological activities. The purpose of this study was to investigate whether AITC regulated Multidrug resistance-associated protein 1 (MRP1), reactive oxide species (ROS) and reduced glutathione (GSH) levels Nrf2 and Notch1 signaling pathways to treat COPD and whether there was an interaction between these two pathways. Lung function indexes and histopathological changes in mice were determined by lung function instrument and HE staining, respectively. The protein expression was analyzed using immunohistochemistry and Western blotting. The mRNA expression was measured by RT-PCR in human bronchial epithelial cell line 16HBE. The contents of ROS, GSH and GSSG were detected by kits in 16HBE cells. The protein expression of Notch1, Hes1, MRP1, Nrf2, and HO-1 in lung tissues of WT mice and untransfected cells were significantly down-regulated in COPD, then significantly ameliorated in treatment groups. The protein expression of MRP1, Notch1 and Hes1 in lung tissues of Nrf2 mice were markedly reduced. There was a significant reduction in expression of Nrf2, HO-1 and MRP1 in si-Notch1 transfected cells. Pretreatment with AITC markedly improved oxidative stress and GSH-redox disorder in COPD. Our study demonstrates that there is a potential interaction between Nrf2 and Notch1 signaling pathways during treatment of COPD.

中文翻译：

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异硫氰酸烯丙酯治疗通过 Nrf2-Notch1 信号传导和 MRP1 上调缓解慢性阻塞性肺疾病


慢性阻塞性肺疾病（COPD）是世界范围内发病率和死亡率较高的疾病，可造成严重的社会和经济负担。异硫氰酸烯丙酯（AITC）是最常见的天然异硫氰酸酯之一，已被证明具有抗炎和抗氧化生物活性。本研究的目的是探讨 AITC 是否通过调节多药耐药相关蛋白 1 (MRP1)、活性氧化物 (ROS) 和还原型谷胱甘肽 (GSH) 水平 Nrf2 和 Notch1 信号通路来治疗 COPD，以及这些信号通路之间是否存在相互作用两条途径。分别采用肺功能仪和HE染色测定小鼠肺功能指标和组织病理学变化。使用免疫组织化学和蛋白质印迹分析蛋白质表达。通过RT-PCR测量人支气管上皮细胞系16HBE中的mRNA表达。采用试剂盒检测16HBE细胞中ROS、GSH、GSSG的含量。 WT小鼠肺组织和未转染细胞中Notch1、Hes1、MRP1、Nrf2和HO-1的蛋白表达在COPD中显着下调，然后在治疗组中显着改善。 Nrf2小鼠肺组织中MRP1、Notch1、Hes1蛋白表达量明显降低。 si-Notch1 转染细胞中 Nrf2、HO-1 和 MRP1 的表达显着降低。 AITC 预处理显着改善 COPD 患者的氧化应激和 GSH 氧化还原紊乱。我们的研究表明，在 COPD 治疗过程中，Nrf2 和 Notch1 信号通路之间存在潜在的相互作用。